Rishik Puppala

Background:  Carotid artery disease is an atherosclerotic condition where there is lipid (LDLs mainly) and molecular buildup in vasculature. Outcomes can typically be severe and in some cases cause stroke which is the primary cause of death, dementia, and disability. Risk factors include age, men, smokers, diet, diabetes, hypertension, and genetics. Collateral circulation with the Circle of Willis leads to an asymptomatic version of the disease, despite the severity of outcome remaining the same.^1,2 In current clinical practice, asymptomatic conditions of this disease are hard to identify, even in patients with increased risk factors. While inflammatory markers can identify disease, clinically, there are no current ways of diagnosing the condition.

Research Objectives:  This review brings together research regarding an inflammatory marker, high serum C-reactive protein (hs-CRP), and the role it can play in prevention of disease progression.

Methods:  A literature review was conducted through PubMed’s Literature Database to look for novel ways to identify serum biomarkers in disease progression of atherosclerosis. Some search terms used combined “atherosclerosis,” “carotid artery disease,” and “carotid artery plaque.” Additionally, “serum biomarkers” and “diagnosis” were combined with the disease state terms to develop a thorough background search on the disease progression.

Results:  hs-CRP levels of subjects were measured at a preliminary screening and separated based on levels in serum. Over the next 5 years, ultrasounds measured plaque increase and found a direct association between hs-CRP levels and carotid artery plaque.³ The study measured Lipoprotein A (LDL) levels and hs-CRP levels and identified a relationship between elevated LDL levels and hs-CRP.⁴ CRP levels increase in serum as a result of transcytosis of endothelial cells when levels in tissue are elevated.⁵ NLRP3  inflammasome activation propagates increased levels of LDLs in subendothelial levels of blood vessels.⁶ Early on prevention by a dual drug therapy of atorvastatin and amlodipine therapy have been shown to show promising results in both plaque volume and hs-CRP levels. However, later intervention only contributes to hs-CRP levels.⁷

Conclusion:  hs-CRP levels are indicative of cardiac inflammation in subjects with atherosclerosis that are asymptomatic.³ Clinically, the results of these studies show that there are serum biomarkers that can identify early diagnosis of atherosclerosis. Depending on the severity, pharmacological agents can be prescribed. A combination of therapy measuring serum lipid markers, hs-CRP, and elevated risk factors could be useful to diagnose asymptomatic patients.

Work Cited:

1. Puig N, Jiménez-Xarrié E, Camps-Renom P, Benitez S. Search for Reliable Circulating Biomarkers to Predict Carotid Plaque Vulnerability. Int J Mol Sci. Nov 3 2020;21(21)doi:10.3390/ijms21218236
2. Heck D, Jost A. Carotid stenosis, stroke, and carotid artery revascularization. Progress in Cardiovascular Diseases. 2021/03/01/ 2021;65:49-54. doi:https://doi.org/10.1016/j.pcad.2021.03.005
3. Xu R, Zhang Y, Gao X, Wan Y, Fan Z. High-sensitivity CRP (C-reactive protein) is associated with incident carotid artery plaque in Chinese aged adults. Stroke. 2019;50(7):1655-1660.
4. Zhang W, Speiser JL, Ye F, et al. High-sensitivity C-reactive protein modifies the cardiovascular risk of lipoprotein (a) multi-ethnic study of atherosclerosis. Journal of the American College of Cardiology. 2021;78(11):1083-1094.
5. Li H-Y, Liu X-L, Liu Y-T, et al. Matrix sieving-enforced retrograde transcytosis regulates tissue accumulation of C-reactive protein. Cardiovascular Research. 2018;115(2):440-452. doi:10.1093/cvr/cvy181
6. Bian F, Yang X-Y, Xu G, Zheng T, Jin S. CRP-Induced NLRP3 Inflammasome Activation Increases LDL Transcytosis Across Endothelial Cells. Original Research. Frontiers in Pharmacology. 2019-January-30 2019;10doi:10.3389/fphar.2019.00040
7. Sakata K, Gamou T, Tada H, Hayashi K, Ino H, Yamagishi M. Low Baseline High-Sensitive C-Reactive Protein is Associated with Coronary Atherosclerosis Regression: Insights from the MILLION Study. J Atheroscler Thromb. May 1 2019;26(5):442-451. doi:10.5551/jat.44255